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Purpose: We conducted a phase I trial of the addition of sorafenib to a chemoradiotherapy regimen in patients with high-risk (intermediate/high grade, >5 cm) extremity soft tissue sarcoma undergoing limb salvage surgery. We conducted a correlative study of quantitative dynamic contrast-enhanced MRI (DCE-MRI) to assess response to treatment. Experimental Design: Patients were treated at increasing dose levels of sorafenib (200 mg daily, 400 mg daily, 400 mg twice daily) initiated 14 days before three preoperative and three postoperative cycles of epirubicin/ifosfamide. Radiation (28 Gy) was administered during cycle 2 with epirubicin omitted. The primary objective was to determine the maximum tolerated dose (MTD) of sorafenib. DCE-MRI was conducted at baseline, after 2 weeks of sorafenib, and before surgery. The imaging data were subjected to quantitative pharmacokinetic analyses. Results: Eighteen subjects were enrolled, of which 16 were evaluable. The MTD of sorafenib was 400 mg daily. Common grade 3–4 adverse events included neutropenia (94%), hypophosphatemia (75%), anemia (69%), thrombocytopenia (50%), and neutropenic fever/infection (50%). Of note, 38% developed wound complications requiring surgical intervention. The rate of ≥95% histopathologic tumor necrosis was 44%. Changes in DCE-MRI biomarker ΔKtrans after 2 weeks of sorafenib correlated with histologic response (R2 = 0.67, P = 0.012) at surgery. Conclusion: The addition of sorafenib to preoperative chemoradiotherapy is feasible and warrants further investigation in a larger trial. DCE-MRI detected changes in tumor perfusion after 2 weeks of sorafenib and may be a minimally invasive tool for rapid assessment of drug effect in soft tissue sarcoma. Clin Cancer Res; 19(24); 6902–11. ©2013 AACR.

Glucose enters the endothelium via a non-insulin sensitive GLUT-1 facilitated transporter that transports glucose continuously. Extracellular hyperglycemia is positively correlated with intracellular glucose. As the glucose levels increase, several changes in the glycolytic pathway, tricarboxilic acid cycle and the pentose phosphate pathway occur, all of them leading to an increase of oxygen reactive species (ROS). ROS are capable not only of directly impairing endothelial cells, but also indirectly by activating poly(ADPribose) polymerase, which inhibits glyceraldehyde 3-phosphate dehydrogenase. Further increase in glycloytic intermediates is followed by activation or overexpression of the main pathological pathways of hyperglycemia induced vascular damage: upregulation of glycation end-products, activation of protein kinase C, increased hexosamine pathway, and increased flux through polyol pathway, finally leading to the progressive narrowing and occlusion of the vessels.

In the last years there were many authors that suggest the existence of an association between different components of metabolic syndrome and various cancers. Two important components of metabolic syndrome are hyperglycemia and hyperinsulinemia. Both of them had already been linked with the increased risk of pancreatic, breast, endometrial or prostate cancer. However the correlation of the level of the glucose and insulin with various types and grades of brain tumors remains unclear. In this article we have analysed the values of plasma glucose and insulin in 267 patients, consecutively diagnosed with various types of brain tumors. Our results showed no correlation between the glycemia and brain tumor types or grades. High plasma levels of insulin were found in brain metastasis and astrocytomas while the other types of brain tumors (meningiomas and glioblastomas) had lower levels of the peptide. The levels of insulin were also higher in brain metastasis and grade 3 brain tumors when compared with grade 1, grade 2 and grade 4 brain tumors.

This study aims to assess the utility of quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters in comparison with imaging tumor size for early prediction and evaluation of soft tissue sarcoma response to preoperative chemoradiotherapy. In total, 20 patients with intermediate- to high-grade soft tissue sarcomas received either a phase I trial regimen of sorafenib + chemoradiotherapy (n = 8) or chemoradiotherapy only (n = 12), and underwent DCE-MRI at baseline, after 2 weeks of treatment with sorafenib or after the first chemotherapy cycle, and after therapy completion. MRI tumor size in the longest diameter (LD) was measured according to the RECIST (Response Evaluation Criteria In Solid Tumors) guidelines. Pharmacokinetic analyses of DCE-MRI data were performed using the Shutter-Speed model. After only 2 weeks of treatment with sorafenib or after 1 chemotherapy cycle, Ktrans (rate constant for plasma/interstitium contrast agent transfer) and its percent change were good early predictors of optimal versus suboptimal pathological response with univariate logistic regression C statistics values of 0.90 and 0.80, respectively, whereas RECIST LD percent change was only a fair predictor (C = 0.72). Post-therapy Ktrans, ve (extravascular and extracellular volume fraction), and kep (intravasation rate constant), not RECIST LD, were excellent (C &gt, 0.90) markers of therapy response. Several DCE-MRI parameters before, during, and after therapy showed significant (P &lt, 05) correlations with percent necrosis of resected tumor specimens. In conclusion, absolute values and percent changes of quantitative DCE-MRI parameters provide better early prediction and evaluation of the pathological response of soft tissue sarcoma to preoperative chemoradiotherapy than the conventional measurement of imaging tumor size change.

Measuring and calibrating relations between cluster observables is critical for resource-limited studies. The mass-richness relation of clusters offers an observationally inexpensive way of estimating masses. Its calibration is essential for cluster and cosmological studies, especially for high-redshift clusters. Weak gravitational lensing magnification is a promising and complementary method to shear studies, that can be applied at higher redshifts. We employed the weak lensing magnification method to calibrate the mass-richness relation up to a redshift of 1.4. We used the Spitzer Adaptation of the Red-Sequence Cluster Survey (SpARCS) galaxy cluster candidates ($0.21.0$ is 4.1$\sigma$; for the entire cluster sample we obtained an average M$_{200}$ of $1.28^{+0.23}_{-0.21}$ $\times 10^{14} \, \textrm{M}_{\odot}$. Our measurements demonstrated the feasibility of using weak lensing magnification as a viable tool for determining the average halo masses for samples of high redshift galaxy clusters. The results also established the success of using galaxy over-densities to select massive clusters at $z > 1$. Additional studies are necessary for further modelling of the various systematic effects we discussed., Comment: 13 pages, 13 figures, accepted for publication in A&A

Despite of high research efforts, ischemic stroke is the leading cause of adult disability worldwide, with enormous social and economic impact. To decrease the devastating impact of ischemic stroke on society, the researchers continue to seek strategies to achieve better functional recovery in stroke victims. This article reviews in detail the actual stage of research effort to develop new strategies in stem cells field, as well as stem cells delivery time course in closed relation with delivery route, stem cells origin, and the local microenvironment. In addition, ischemic stroke occurs in older people with comorbidities that may limit benefit and many preclinical studies did not take into account this. However, sustained research funding is mandatory to allow neuroscientist to develop and test new ways to improve the economic impact of stroke consequences on society.

The concept described by the term NoSQL (Not Only SQL) is a database that is distributed, may not require fixed table schemas, usually avoids join operations and is typically horizontally scalable, it does not offer SQL query interface and is available in most cases as open source - some bibliographic sources use the term to refer to a completely unrelated system. This concept is also assimilated by sources in the academic world as a structured form of storage. The two terms seem not to be entirely equivalent; relational databases, for example, also meet the official definition of data storage structures, but they are somewhat opposite qualities to the concept of NoSQL. The aim of this paper is to discuss the challenges met by the NoSQL solutions and to propose solutions for these challenges.

Teaching disciplines involving mathematical modeling, simulation, statistics and data analysis can be approached in an attractive manner for students (from specialization such as Informatics) if the teacher appeals to visual programming environments. For statistical modeling and simulation, programming skills allow implementation of Windows applications with user friendly interface, with graphical representations and easy to interpret results. The objective of this paper is to present the facilities of a modern visual programming environment (Microsoft Visual C#), for teaching in an attractive way applications for generating random variables, statistical indicators calculation or empirical probabilities calculation. As a case study is presented the development of an application that models a real-life problem. It is considered that the time (in years) of operation for an equipment has a negative exponential distribution of parameter lambda. We are interested in mean time of functioning and the probability that an equipment will function properly after a number of years. In a first step, using visual components, graphical interface of the application is built. Using methods for generating random variables (inverse method or rejection method) there are simulated functioning times with a negative exponential distribution. Some statistical indicators, such as mean or variance are calculated and the probability of various events are calculated empirically by approximation with frequency. Values obtained through modeling and simulation are compared with theoretical values (mean, frequency, percentile). The research concludes that a visual programming environment has tools that allow a programmer implementation of more complex applications than those generally made using a specialized software for statistical analysis.

Three dimensional bilateral imaging is the standard for most clinical breast dynamic contrast-enhanced (DCE) MRI protocols. Because of high spatial resolution (sRes) requirement, the typical 1–2 min temporal resolution (tRes) afforded by a conventional full-k-space-sampling gradient echo (GRE) sequence precludes meaningful and accurate pharmacokinetic analysis of DCE time-course data. The commercially available, GRE-based, k-space undersampling and data sharing TWIST (time-resolved angiography with stochastic trajectories) sequence was used in this study to perform DCE-MRI exams on thirty one patients (with 36 suspicious breast lesions) before their biopsies. The TWIST DCE-MRI was immediately followed by a single-frame conventional GRE acquisition. Blinded from each other, three radiologist readers assessed agreements in multiple lesion morphology categories between the last set of TWIST DCE images and the conventional GRE images. Fleiss’ κ test was used to evaluate inter-reader agreement. The TWIST DCE time-course data were subjected to quantitative pharmacokinetic analyses. With a four-channel phased-array breast coil, the TWIST sequence produced DCE images with 20 s or less tRes and ~ 1.0×1.0×1.4 mm3 sRes. There were no significant differences in signal-to-noise (P = 0.45) and contrast-to-noise (P = 0.51) ratios between the TWIST and conventional GRE images. The agreements in morphology evaluations between the two image sets were excellent with the intra-reader agreement ranging from 79% for mass margin to 100% for mammographic density and the inter-reader κ value ranging from 0.54 (P < 0.0001) for lesion size to 1.00 (P < 0.0001) for background parenchymal enhancement. Quantitative analyses of the DCE time-course data provided higher breast cancer diagnostic accuracy (91% specificity at 100% sensitivity) than the current clinical practice of morphology and qualitative kinetics assessments. The TWIST sequence may be used in clinical settings to acquire high spatiotemporal resolution breast DCE-MRI images for both precise lesion morphology characterization and accurate pharmacokinetic analysis.

Type 2 Diabetes and its Implications in Cerebrovascular DiseaseType 2 diabetes represents an independent risk factor for vascular cerebral pathology, with a 2-3 times greater probability of stroke. The number of diabetic patients with stroke increased substantially from 6.2% to 11.3% during 1996-2006. Ischemic stroke, small or large vessels occlusion, is the main subtype of cerebrovascular disease, while a smaller percentage is attributed to cerebral hemorrhage. Hyperglycemia and hyperinsulinemia, excess free fatty acids, prothrombotic state cause endothelial dysfunction with blood flow disturbance and major cerebral vessels injury. Elevated blood sugar levels are also associated with a poor prognosis during post-stroke phase. From the total number of deaths caused by acute cerebrovascular events, 16% for men and 33% for women are due to diabetes.

This paper intends to present one of the studies we jointly done during the research for our Ph.D. theses. Cristian Bucur`s thesis aim is to study how the knowledge stored in web pages from various sources can be retrieved and classified. Bogdan Tudorica`s thesis aim is to study the ways to manage large quantities of data for various purposes (especially through use of new technologies, such as NoSQL databases. As such, the application we are describing in this paper is a mixed one, containing both web page crawling and parsing and data storage in a commonly used NoSQL database.

Matrix metalloproteinases (MMPs) are well-recognized denominators for extracellular matrix remodeling in the pathology of both ischemic and hemorrhagic strokes. Recent data on non-nervous system tissue showed intracellular and even intranuclear localizations for different MMPs, and together with this, a plethora of new functions have been proposed for these intracellular active enzymes, but are mostly related to apoptosis induction and malign transformation. In neurons and glial cells, on human tissue, animal models and cell cultures, different active MMPs have been also proven to be located in the intra-cytoplasmic or intra-nuclear compartments, with no clear-cut function. In the present study we show for the first time on human tissue the nuclear expression of MMP-9, mainly in neurons and to a lesser extent in astrocytes. We have studied ischemic and hemorrhagic stroke patients, as well as aged control patients. Age and ischemic suffering seemed to be the best predictors for an elevated MMP-9 nuclear expression, and there was no evidence of a clear-cut extracellular proteolytic activity for this compartment, as revealed by intact vascular basement membranes and assessment of vascular densities. More, the majority of the cells expressing MMP-9 in the nuclear compartment also co-expressed activated-caspase 3, indicating a possible link between nuclear MMP-9 localization and apoptosis in neuronal and glial cells following an ischemic or hemorrhagic event. These results, besides showing for the first time the nuclear localization of MMP-9 on a large series of human stroke and aged brain tissues, raise new questions regarding the unknown spectrum of the functions MMPs in human CNS pathology.

To assess the accuracy of the shutter-speed approach compared with standard approach dynamic contrast material-enhanced magnetic resonance (MR) imaging pharmacokinetic analysis for breast cancer diagnosis.This study was approved by the institutional review board and was HIPAA compliant. Informed consent was obtained from 89 high-risk women (age range, 28-83 years) who had 92 suspicious lesions with negative findings at mammography (but visible at MR imaging). Each underwent a research dynamic contrast-enhanced MR imaging examination just prior to a clinical MR imaging-guided interventional procedure. Tumor region of interest (ROI) averaged and (for some) pixel-by-pixel dynamic contrast-enhanced time-course data, together with mean arterial input function, were subjected to serial standard and shutter-speed approach analyses to extract pharmacokinetic parameters, including rate constant for passive contrast reagent transfer between plasma and interstitium (K(trans)) and interstitial space volume fraction, or v(e). Pathologic findings were used as reference standards. Diagnostic accuracy was assessed with receiver operating characteristic analyses.The pathologic analyses revealed 20 malignant and 72 benign lesions. Positive predictive value of the institutional clinical breast MR imaging protocol was 22%. At 100% sensitivity, ROI-averaged shutter-speed approach K(trans) had significantly (P = .008) higher diagnostic specificity than standard approach K(trans): 86.1% versus 77.8%. The difference in the ROI-averaged K(trans) parameter value, or ΔK(trans) (≡ K(trans) [shutter-speed approach] - K(trans) [standard approach]), had even higher specificity (88.9%). Combined use of ROI analysis and pixel-by-pixel mapping of ΔK(trans) achieved 98.6% specificity at 100% sensitivity.The use of the shutter-speed dynamic contrast-enhanced MR imaging method has the potential to improve breast cancer diagnostic accuracy and reduce putatively unnecessary biopsy procedures that yield benign pathologic findings.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11102413/-/DC1.

An aeromycological study to identify and quantify allergenic fungi and their fluctuations was conducted at Timisoara. The diversity of the aeromycoflora in this study, based on the recovery of fungal propagules by the volumetric sampling method was conducted for 30 days using the Lanzoni sampler. The study showed that the most prevalent (major components) fungal spores in the air of Timisoara were Cladosporium spp., Drechslera/Helminthosporium spp., Alternaria spp. and Epicoccum spp. The abundant genera were Cladosporium, Fusarium/Leptosphaeria, Drechslera/Helminthosporium, Alternaria and Torula. Cladosporium was the most abundant fungal spore type (41%) collected throughout the period of study reaching.

A range of commercially available dietary fibres (DFs), representing both insoluble and soluble forms, were used in the production of pasta. Addition of fibre was at a range of levels (2.5-10%). The potential glycaemic index of these pastas was then evaluated using an in vitro model system to determine starch digestibility and sugar release. Scanning electron microscopy was used to relate structural properties of the pasta to starch degradation. The resulting predicted glycaemic indexes illustrated that the inclusion of DFs into pasta can reduce the glycaemic index of an already low GI food by up to 40%. As such, compared to the predicted glycaemic index value for the control fresh pasta (GI = 45), inclusion of pea fibre, guar gum and locust bean gum yielded pasta with GI values of 39.2, 37.9 and 37 respectively. Thus the type of dietary fibre used was important in the rate of starch digestion observed during the in vitro process. Equally, the level of fibre inclusion was of importance with an inclusion rate of 2.5% generally resulting in pasta with a predictive GI of 42.1, whereas an inclusion of 10% yielded pasta with a GI value of 37.2. Such reductions could be achieved through a number of possible mechanisms including antagonistic and synergistic relationships existing between DF's and other food components, the effect of DF's in entrapping pasta particles and thus inhibiting starch degradation, and the restriction of water movement during the cooking of pasta products, thus indicating that starch swelling is impaired.

Objective. Our study was designed to assess the cognitive impairment after ischemic stroke and to study its correlation with poststroke depression. Methods. We studied a series of 94 consecutive patients (45 men and 49 women, mean age 68,9 years) with acute first-ever ischemic stroke. The patients underwent a neurological and neuropsychological examination at baseline, after 6 months and after 12 months. For the cognitive assessment we used Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) and for the evaluation of depression we used Hamilton Depression Rating Scale (HDRS). Results. Depression was diagnosed in 48 patients (49%) at 6 months and in 55 of the patients (54%) at 12 months after ischemic stroke. The cognitive impairment was higher at 12 months than at 6 months; the depressive patients had more severe cognitive impairment than the nondepressive patients. Conclusions. A lot of patients suffer from depression after stroke, and the frequency of depression seems to increase during the first year. The post stroke depression (PSD) is correlated with the cognitive impairment. We emphasize the importance of psychiatric assessment of stroke patients.

Evaluation of mild cognitive impairment is important for early management in order to prevent severe dementia. The goal of our study was to assess the cognitive state in patients with ischemic vascular events (first ever stroke or transient ischemic attack).We studied 86 patients who were hospitalized in The Clinic of Neurology from Craiova during the year 2007, for first ever stroke (56 patients) or transient ischemic attack (TIA-32 patients) and also a group composed of 92 control subjects without signs of cerebrovascular disease but with vascular risk factors present. We used for the assessment two scales: Mini Mental State Examination (MMSE) and Cambridge Cognitive Examination (CAMCOG). We made assessment at baseline, after 3 months respectively 6 months. We performed computed tomography in both groups, for a correct diagnosis. At baseline the patient group had a mean MMSE score 27,3 and a mean CAMCOG score 93,9. The control subjects had a mean MMSE score 28,5 and a mean CAMCOG score 96,8. After 6 months the patient group showed a mean MMSE score 25,4 and CAMCOG score 81,9. The control subjects showed a mean MMSE score 26,6 and CAMCOG score 88,95. The patients with cerebrovascular events showed a higher cognitive impairment than the control subjects. Patients with stroke presented a greater cognitive impairment than TIA patients. In subjects with cerebrovascular risk factors we observed the cognitive decline even before the cerebrovascular events became clinically evident.

Summary Barley beta-glucan, partially hydrolysed guar gum and inulin were used in the processing of low-fat yoghurts. The possible beneficial effects of carbohydrate fat replacers on the rheological, textural and sensory quality of low-fat yoghurt-based products were determined. Comparisons were made between the sample yoghurts made from a low-fat milk base, and full-fat and low-fat yoghurt controls. The inclusion of the carbohydrate components reduced product syneresis and improved the texture and rheological properties of the low-fat-based products so that their quality characteristics were similar to yoghurt made with full-fat milk. Both the type and also the amount of carbohydrate component altered product characteristics. Beta-glucan addition at low level (0.5%) was effective in improving serum retention of the yoghurt and its viscoelastic nature (G′, G′ and tan δ). In contrast, higher levels (above 2%) of inulin and guar gum were needed to exert significant improvements in the textural characteristics of yoghurt. Sensory analysis conducted on the samples illustrated that the inclusion of carbohydrate-based fat replacers could be successfully utilised to mimic full-fat products.

Dynamic contrast-enhanced MRI (DCE-MRI) has been widely used in tumor detection and therapy response evaluation. Pharmacokinetic analysis of DCE-MRI time-course data allows estimation of quantitative imaging biomarkers such as Ktrans(rate constant for plasma/interstitium contrast reagent (CR) transfer) and ve (extravascular and extracellular volume fraction). However, the use of quantitative DCE-MRI in clinical prostate imaging islimited, with uncertainty in arterial input function (AIF, i.e., the time rate of change of the concentration of CR in the blood plasma) determination being one of the primary reasons. In this multicenter data analysis challenge to assess the effects of variations in AIF quantification on estimation of DCE-MRI parameters, prostate DCE-MRI data acquired at one center from 11 prostate cancer patients were shared among nine centers. Each center used its site-specific method to determine the individual AIF from each data set and submitted the results to the managing center. Along with a literature population averaged AIF, these AIFs and their reference-tissue-adjusted variants were used by the managing center to perform pharmacokinetic analysis of the DCE-MRI data sets using the Tofts model (TM). All other variables including tumor region of interest (ROI) definition and pre-contrast T1 were kept the same to evaluate parameter variations caused by AIF variations only. Considerable pharmacokinetic parameter variations were observed with the within-subject coefficient of variation (wCV) of Ktrans obtained with unadjusted AIFs as high as 0.74. AIF-caused variations were larger in Ktrans than ve and both were reduced when reference-tissue-adjusted AIFs were used. The parameter variations were largely systematic, resulting in nearly unchanged parametric map patterns. The CR intravasation rate constant, kep (= Ktrans/ve), was less sensitive to AIF variation than Ktrans (wCV for unadjusted AIFs: 0.45 for kep vs. 0.74 for Ktrans), suggesting that it might be a more robust imaging biomarker of prostate microvasculature than Ktrans.

Malignant glioma therapy represent one of the greatest challenges in neuro-oncology. Despite technical advances in neurosurgery, radiotherapy and chemotherapy the prognosis of most patients remains very poor. Advances in understanding the molecular mechanisms involved in malignant glioma pathogenesis helped researchers to develop new agents that target the genetic and cellular alterations. This review presents the targeted agents used in research and clinical trials for malignant glioma treatment.

Nonstarch polysaccharides (NSPs), both soluble and insoluble, were added to pasta doughs at levels of 2.5%, 5%, 7.5%, and 10% levels. The cooking and textural characteristics of the pastas were evaluated using a range of analytical techniques. Generally, NSP addition was found to increase the cooking losses, and reduce the protein and starch contents of the pasta. This effect was dependent on the level of NSP added and also the type (soluble or insoluble). Pasta firmness was generally reduced in relation to the level of NSP addition, although some gel-forming NSPs resulted in higher firmness values. Pasta stickiness, adhesiveness, and elasticity were also affected. The results indicate that careful selection of NSP addition is needed to ensure optimum textural and cooking characteristics in NSP enriched pasta products.